Iodonium ylide-mediated radiofluorination of 18F-FPEB and validation for human use

J Nucl Med. 2015 Mar;56(3):489-92. doi: 10.2967/jnumed.114.151332. Epub 2015 Feb 5.

Abstract

Translation of new methodologies for labeling nonactivated aromatic molecules with (18)F remains a challenge. Here, we report a one-step, regioselective, metal-free (18)F-labeling method that uses a hypervalent iodonium(III) ylide precursor, to prepare the radiopharmaceutical (18)F-3-fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile ((18)F-FPEB).

Methods: Automated radiosynthesis of (18)F-FPEB was achieved by reaction of the ylide precursor (4 mg) with (18)F-Et4NF in dimethylformamide at 80°C for 5 min and formulated for injection within 1 h.

Results: (18)F-FPEB was synthesized in 20% ± 5% (n = 3) uncorrected radiochemical yields relative to (18)F-fluoride, with specific activities of 666 ± 51.8 GBq (18 ± 1.4 Ci)/μmol at the end of synthesis and was validated for human use.

Conclusion: Radiofluorination of iodonium (III) ylides proved to be an efficient radiosynthetic strategy for synthesis of (18)F-labeled radiopharmaceuticals.

Keywords: 18F-FPEB; PET; fluorination; iodonium ylide; mGlu5.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Automation
  • Electrons
  • Fluorine Radioisotopes / chemistry*
  • Humans
  • Hydrolysis
  • Iodine / chemistry*
  • Nitriles / chemistry*
  • Onium Compounds / chemistry*
  • Oxygen / chemistry
  • Positron-Emission Tomography
  • Pyridines / chemical synthesis
  • Pyridines / chemistry*
  • Radiochemistry
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / chemistry
  • Temperature
  • Time Factors

Substances

  • 3-fluoro-5-((pyridin-3-yl)ethynyl)benzonitrile
  • Fluorine Radioisotopes
  • Nitriles
  • Onium Compounds
  • Pyridines
  • Radiopharmaceuticals
  • Iodine
  • Oxygen